Site-specific and general recombination are fundamental processes throughout nature. They are important in maintaining genetic diversity, regulation of expression, transposition, generation of the repertoire of antibodies, and the integration of viruses into the host chromosome. General recombination and double-stranded break repair are two ways of looking at the same event. It has become clear that human diseases, including some types of cancer, result from the failure to repair damage to DNA. This application focuses on the unique aspect of recombination of synapsis, the juxtaposition of like sequences on the surface of the recombinase. We will investigate the detailed structure of gamma/delta resolvase synaptic complex, the topology of synapsis by phage lambda integrative and excisive recombination, the stages in synapsis by the Escherichia coli RecA protein, and the mechanism of synapsis by yeast Sep1. The latter two are general recombination proteins, and the former are site-specific recombinases. We will investigate the means by which synapsis of the proper sequences is brought about in the face of a vast excess of competitor sequences. A critical aspect of synapsis inside a living cell is the effective concentration of DNA, a parameter that measures the net propensity of DNA to interact with other DNA or proteins. We will use the activity of recombinases in E. coli to study the effective concentration of DNA and to determine the factors that influence it.